The broad, long-term objective of this proposal is to establish quantitative ultrasonography (QUS) as an objective, accurate, precise, and widely available method for diagnosis and grading of hepatic steatosis in the over 100 million persons in the United States and over one billion persons worldwide with or at risk for non-alcoholic fatty liver disease (NAFLD). The immediate goal of our research is to refine and prospectively validate QUS technology to diagnose and grade hepatic steatosis in NAFLD. As part of this validation and as supported by our preliminary studies, we will show that QUS is superior to conventional ultrasonography (CUS), the current most commonly used modality, for diagnosis and grading. To achieve this goal, we propose a prospective, cross-sectional clinical study in adult patients undergoing contemporaneous clinical-care liver biopsy for evaluation of suspected NAFLD or re-assessment of previously diagnosed NAFLD. Patients will undergo same-day QUS and CUS research examinations within 60 days of percutaneous liver biopsy; liver biopsies will be scored histologically for presence and grade of hepatic steatosis. Subsets of patients will undergo repeated QUS and CUS examinations on the same day or on different days, sometimes varying either sonographer or scanner. In parallel with the clinical study, the QUS technology will be tailored for adult liver to refine and thus improve accuracy and precision of QUS parameters. The central hypothesis of this proposal is that QUS is superior to CUS for diagnosis and grading of hepatic steatosis in NAFLD. The study has the following specific aims: Specific Aim 1. Accuracy for diagnosing hepatic steatosis. Hypothesis: QUS is more accurate than CUS for diagnosing the presence of hepatic steatosis in adult patients with suspected or known NAFLD, using contemporaneous liver biopsy and centrally scored histology as reference. Patient acquisition and data analysis factors that affect diagnostic accuracy of QUS and CUS will be examined. Specific Aim 2. Accuracy for grading hepatic steatosis. Hypothesis: QUS is more accurate than CUS for grading the degree of hepatic steatosis in adult patients with suspected or known NAFLD, using contemporaneous liver biopsy and centrally scored histology as reference. Patient acquisition and data analysis factors that affect grading accuracy of QUS and CUS will be examined. Specific Aim 3. Repeatability-reproducibility. Hypothesis: QUS provides higher (a) same-day repeatability, (b) between-day repeatability, (c) inter-sonographer reproducibility, and (d) inter-scanner-manufacturer reproducibility than CUS in adult patients with suspected or known NAFLD. Patient acquisition and data analysis factors that affect repeatability-reproducibility of QUS and CUS will be examined.